It is known that fungi infect man, animals, and plants to cause various diseases. In man, for instance, some fungi cause superficial mycosis of the skin and mouth cavity, while others cause systemic mycosis of the viscera and brain or the like. Fungi also cause similar infectious diseases in pet animals and livestock. There also are fungi which induce various diseases in crop plants such as orchard trees and vegetables.
Among those pathogenic fungi which cause systemic mycosis in man are fungal species of the genera Candida, Cryptococcus, and Aspergillus. Referring to superficial mycosis, candidal species which infect the skin, mouth cavity, and vagina, trichophytons infecting the skin of the limbs (the causative organisms of athlete's foot), and Malassezia species (the causative organisms of tinea versicolor) are regarded as representative pathogenic fungi. In addition to those fungi, a variety of other fungi also inhabit the earth 's ecology and suspected to do harm to animals and plants.
Recent years have seen a dramatic increase in the incidence of allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis. The pathogenesis of many of those allergic diseases is generally explained as follows. As the host is sensitized by a disease-inducing antigen, an IgE antibody (reagin) specific to antigen, i.e. allergen, is produced in the host's serum and tissues. As the host is reexposed to the allergen, the IgE coupled to the mast cells or basophils and the specific allergen form complexes and the IgE-complex crosslinks on the cell surface, and triggers physiological events arising from IgE-antigen interactions. Substances known as chemical mediators are involved in those physiological events.
Some of them are the chemical mediators preexisting in the granules of mast cells and eosinophils but released extracellularly by degranulation upon activation, such as histamine, serotonin, eosinophilic factors, etc., while others are synthesized de novo by the activation of mast cells. As to the latter mediators, activation of phospholipase A.sub.2 entails activation of lipoxigenase and cyclooxigenase which act upon the arachidonic acid derived from the membrane phospholipid to produce various leukotrienes and thromboxanes. Those chemical mediators cause long-term allergic inflammentions such as contraction of bronchial smooth muscle and mucosal edema, or the like. Those events may be either systemic or local according to the route by which the antigen enters into the body and the pattern of deposition of IgE on the mast cells or basophils. The local symptoms generally occur on the surface of the epithelium at the site of entry of the allergen. The systemic event includes anaphylactic shock which is the result of response of the IgE-basophil to the antigen in the vasculature.
There are many allergic diseases in which various substances in the environment, inclusive of ticks and pollens, and antigenic substances contained in foods act as allergens. Among them, allergic diseases caused by fungi are also numerous and allergens derived from fungi of various genera such as Candida, Aspergillus, Alternaria, Cladosporium, Malassezia, and Penicillium act as the etiologic factors.
Few antifungal agents are known today which can be used in the treatment and prevention of those fungal infections and contaminations for which such fungi are responsible. Among those agents, amphotericin B, flucytosine, miconazole, fluconazole, etc. can be mentioned as therapeutic agents for systemic infections in men and animals. However, those substances are not fully satisfactory in efficacy, toxicity, and/or antibacterial spectrum and have not proved sufficiently useful as therapeutic agents.
Meanwhile, there are various kinds of therapeutic agents for allergic diseases, such as lipoxigenase inhibitors which inhibit production of said various chemical mediators, thromboxane synthase inhibitors, antihistaminics which antagonize the chemical mediator, and leukotriene receptor antagonists. In addition, steroids not only inhibit production of chemical mediators but have various physiological activities, thus being the most important of antiallergic agents.